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It takes a team: reflections on insecticide discoveries, toxicological problems and enjoying the unexpected
Author(s) -
Wing Keith D
Publication year - 2017
Publication title -
pest management science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.296
H-Index - 125
eISSN - 1526-4998
pISSN - 1526-498X
DOI - 10.1002/ps.4311
Subject(s) - adme , bioavailability , agrochemical , toxicodynamics , drug discovery , pharmacology , biochemical engineering , microbiology and biotechnology , chemistry , computational biology , business , biology , pharmacokinetics , biochemistry , engineering , ecology , toxicokinetics , agriculture
Absorption/distribution/metabolism/excretion ( ADME )‐related studies are mandatory in agrochemical development/registration, but can also play a valuable role in the discovery process. In combination with target‐site potency, bioavailability/ ADME characteristics determine agrochemical bioactivity and selectivity, and these concerns can dictate the fate of a discovery lead area. Bioavailability/ ADME research was critical to the eventual commercialization of three different insecticide chemistries examined in this paper. In one situation, improved systemicity in anthranilic diamides was required to expand pest spectrum. In another, ADME tools were needed to improve the selective toxicity and non‐target safety of sodium channel blocker insecticides. Finally, differential ADME characteristics of two classes of hormone agonists dictated differential insecticidal activity, and were useful in optimizing the dibenzoylhydrazine ecdysone agonists. ADME discovery research will help companies to advance novel, efficacious and selective agrochemicals, but organizational patience and a desire to understand lead areas in depth are required. © 2016 Society of Chemical Industry